Magnetic resonance imaging (MRI) has been developed in recent years and, for improved imaging, paramagnetic contrast agents have been given to patients prior to imaging. A number of patents disclose paramagnetic MRI contrast agents including, for example, U.S. Pat. Nos. 4,647,447; 4,859,451; 4,957,939; 4,963,344; 5,021,236; 5,064,636 and 5,120,527; and PCT application WO 92/21017. These patents are considered to be illustrative of prior references in the field and are not intended to be the most pertinent references.
Paramagnetic agents of the type disclosed in the above patents have been administered to the patient in the form of aqueous solutions. In addition, paramagnetic oil emulsions have been provided for MRI imaging in the gastro-intestinal tract as disclosed in U.S. Pat. Nos. 5,064,636 and 5,120,527. There has been a continuing effort to develop complexes of paramagnetic metal ions as MRI contrast agents that function effectively as organ imaging agents as well as blood pool agents, or for other uses, such as agents for imaging the bone marrow, spleen, liver, or lymph nodes. Liposomes have also been studied as MRI contrast agents, and, more recently, as disclosed in PCT application WO 92/21017, lipo soluble contrast agents may be administered in the form of lipid emulsions. The contrast agents of the PCT application are useful in the imaging of the liver, blood pool and reticuloendothelial system (RES).
Notwithstanding the prior efforts in the field, there is a continuing need for improved MRI contrast agents. In particular, MRI contrast agents are needed which function effectively as organ imaging agents as well as blood pool agents, and for general imaging of the reticuloendothelial system. Stable and versatile MRI contrast agents are needed, especially for intravenous use.